Leptin, a produce of the ob gene, was originally thought to be produced exclusively by adipocytes. Recently, leptin messenger RNA (mRNA) and leptin protein were identified in human placental trophoblast cells, suggesting a potential regulatory role in human pregnancy. In the present study, placental villous tissue was collected upon cesarean section from baboons, an established model for the study of human pregnancy, at early (day 60, n=5), mid (day 100, n=5) and late (day 160, n=5) pregnancy (term=184 days) and leptin mRNA quantitated by competitive RT-PCR. To localize transcripts to specific placental cell types, in situ hybridization was performed. Additionally, maternal blood samples were collected throughout pregnancy via venipuncture and peripheral leptin concentrations determined by RIA. Thus, the expression of leptin mRNA transcripts was detected in all placentas by RT-PCR. In situ hybridization localized leptin transcripts in trophoblastic competitive RT-PCR indicated an approximately seven-fold reduction (P<0.02) in leptin mRNA transcripts between early and late gestation. The abundance (mean+SE) of leptin mRNA declined from 6.8+2.1 at day 60 to 3.5+1.1 at day 100 to 01.+0.3 x 103 attomoles/ l at day 160 of gestation. Maternal leptin levels, which are dramatically higher (P<0.01) than I non-pregnant baboons, increased (P<0.005) approximately three-fold between early and late pregnancy. Thus, concentrations increased from 63.6+10.4 early, to 98.0+10.0 at mid, to 157.8+16.1 ng/ml late in pregnancy. Maternal leptin levels were positively correlated (r=0.66, P<0.001) and placental leptin mRNA levels negatively correlated (r=-0.64, P<0.01) with increasing gestational age. Variations in both maternal peripheral leptin concentrations and placental leptin mRNA abundance may indicate changing regulatory roles for the polypeptide throughout pregnancy and emphasizes the potential of the baboon as a model for leptin action in